Abstract
We analyze the effects of N-terminal acetylation and C-terminal amidation on the cytotoxic properties of β-hairpin antimicrobial peptide tachyplesin I. MTT-assay showed that modified tachyplesin I exhibited increased cytotoxicity toward both tumor and normal human cells. Hemolytic activity of modified tachyplesin I was also higher than that of the initial molecule. In contrast to non-modified tachyplesin I, the peptide with C- and N-terminal modifications is resistant to proteolytic degradation in fresh human serum. C- and N-terminal modifications make tachyplesin I more attractive prototype of anticancer drug due to its more potent cytotoxic effect and better pharmacokinetic properties.
Keywords:
antimicrobial peptides; chemical modification; cytotoxicity; tachyplesin I.
MeSH terms
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A549 Cells
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Acetylation
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Amides / chemistry
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Amino Acid Sequence
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Antimicrobial Cationic Peptides / chemical synthesis
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Antimicrobial Cationic Peptides / toxicity*
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Cell Survival / drug effects
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Cytotoxins / chemical synthesis
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Cytotoxins / toxicity*
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DNA-Binding Proteins / chemical synthesis
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DNA-Binding Proteins / toxicity*
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Erythrocytes / drug effects
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Escherichia coli / genetics
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Escherichia coli / metabolism
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Gene Expression
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HEK293 Cells
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HeLa Cells
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Hemolysis / drug effects
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Humans
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Inhibitory Concentration 50
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Peptides, Cyclic / chemical synthesis
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Peptides, Cyclic / toxicity*
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Protein Stability
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Proteolysis
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Recombinant Proteins / toxicity*
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Solid-Phase Synthesis Techniques / methods*
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Structure-Activity Relationship
Substances
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Amides
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Antimicrobial Cationic Peptides
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Cytotoxins
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DNA-Binding Proteins
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Peptides, Cyclic
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Recombinant Proteins
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tachyplesin peptide, Tachypleus tridentatus